It is highly desirable to understand how enzymes and proteins in general bind to only specific ligands. Realization of this objective leads directly to our being able to design drugs that can bind to different receptors and enzymes with pre-determined affinties. We have been able to predict the structure of enzyme-substrate complexes using conformational energy calculations. We have developed a global search technique that allows us to compute all of the allowed binding modes for substrates at the active sites of enzymes. The strategy is applied to lysozyme where it is shown that we have been able to compute the structures of enzyme-substrate complexes of this enzyme that are in excellent agreement with both X-ray crystallographic and solution studies.